| Summary: | <p>The motor thalamus is a crucial component of the mammalian motor circuit which links subcortical sensorimotor inputs with cortical regions to facilitate ongoing control of movement and behaviour. Thalamocortical neurons from basal ganglia-recipient thalamus (BZ) and cerebellar-recipient thalamus (CZ) preferentially target different layers of motor cortex in rodents. Higher order BZ, comprised of ventral anterior (VA) and ventral medial (VM) thalamic nuclei innervate layer 1 (L1) of frontal cortical areas including motor cortex, and first order CZ, formed of ventral lateral thalamus (VL), innervates deeper layers. The prevailing assumption has been that pyramidal apical tuft dendrites are the exclusive postsynaptic target of BZ axons in L1. However, recent evidence has suggested that L1 elongated neurogliaform cells (ENGCs), which mainly reside in L1a and can be identified by expression of neuron-derived neurotrophic factor (NDNF), are directly targeted by higher order thalamic nuclei in prefrontal cortex and sensory cortical areas. </p>
<p>Here we test the hypothesis that L1 interneurons also receive BZ innervation in motor cortex. Using an NDNF-Cre mouse, we first confirmed with immunohistochemistry that L1 NDNF-expressing (NDNF+) interneurons in motor cortex were GABAergic, and often co-expressed reelin, consistent with being ENGCs. To find out whether these L1 NDNF+ motor cortical interneurons receive direct thalamocortical input, we developed an injection technique to optimise restriction of viral labelling to L1 and demonstrated with monosynaptic retrograde rabies viral tracing that these NDNF+ neurons receive innervation from several thalamic nuclei, especially VM. The same tracing experiments with retinol-binding protein 4 (RBP4)-Cre mice reveal a greater proportion of VL innervation of L5 pyramidal neurons compared with VM. These results suggest that motor thalamus differs not only in its laminar innervation of cortex, but also of its neuronal targets. To explore the physiological influence of ENGCs on the VM thalamocortical pathway in motor cortex, we recorded from both motor cortex and VM in awake mice while optogenetically stimulating VM and inhibiting L1 NDNF+ neurons. We did not see any significant changes in firing rates of cortical neurons, but there was an increase in cortical synchrony in response to suppressing L1 NDNF+ neurons, especially when combined with an increase in VM firing, indicating that a function of ENGCs in motor cortex may be to regulate VM-evoked cortical synchrony.</p>
<p>In addition to these experiments in mice, we also performed neurochemical parcellation of macaque thalamus. This revealed interesting patterns, including complementary patterns of GAD67 and vGluT2 immunostaining in subnuclei of mediodorsal thalamus.</p>
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